Threshold Pharmaceuticals Announces Initiation of TH-302 Phase 3 MAESTRO Study
in Patients With Locally Advanced or Metastatic
Pancreatic Adenocarcinoma
Threshold Earns a $30 Million Milestone Payment From Merck KGaA
SOUTH SAN FRANCISCO, CA -- (Marketwire) -- 01/25/13 -- Threshold
Pharmaceuticals, Inc. (NASDAQ: THLD) today announced that Threshold's
partner Merck KGaA, Darmstadt, Germany, through its division Merck
Serono, initiated the global Phase 3 MAESTRO study assessing the
efficacy and safety of investigational hypoxia-targeted drug TH-302
in combination with gemcitabine in patients with previously
untreated, locally advanced unresectable or metastatic pancreatic
adenocarcinoma. The initiation of the Phase 3 MAESTRO study resulted
in Threshold earning a $30 million milestone payment from Merck KGaA
pursuant to the terms of Threshold's license and co-development
agreement with Merck KGaA, which includes an option for Threshold to
co-commercialize in the U.S. MAESTRO stands for TH-302 in the
treatment of MetastAtic or unrESectable pancreaTic adenocaRcinOma.
MAESTRO is a randomized, placebo-controlled, international,
multi-center, double-blind Phase 3 trial of TH-302 plus gemcitabine
compared with placebo plus gemcitabine and is expected to enroll 660
patients. The primary efficacy endpoint is overall survival; the
secondary endpoints include efficacy measured by progression-free
survival (PFS), overall response rate and disease control rate, as
well as assessments of safety and tolerability, pharmacokinetics and
biomarkers. The study is being conducted under a Special Protocol
Assessment (SPA) with the U.S. Food and Drug Administration (FDA). An
SPA is a review conducted by the FDA on a clinical trial that will
form the primary basis of an efficacy claim in a marketing
application. The FDA provided written agreement that the design and
planned analysis of this study could adequately address objectives in
support of a regulatory submission. However, the determination for
drug approval by the FDA is made after a complete review of a
marketing application and is based on the entire data in the
application. The study design was discussed with the FDA also at an
End of Phase 2 meeting and with the European Medicines Agency (EMA)
during a scientific advice procedure.
TH-302 is an investigational hypoxia-targeted drug that is designed
to be activated under severe tumor hypoxic conditions, a hallmark of
many cancers. Areas of low oxygen levels (hypoxia) in solid tumors
are due to insufficient blood supply as a result of aberrant
vasculature.
"Initiation of the Phase 3 MAESTRO study is an important advancement
in the overall development of TH-302 for the treatment of patients
living with cancer," said Barry Selick, Ph.D., Chief Executive
Officer of Threshold. "This marks the second Phase 3 study of TH-302
in addition to the ongoing Phase 3 pivotal trial in patients with
soft tissue sarcoma. In addition, we continue to explore the
potential breadth and activity of TH-302 against a variety of solid
tumors and hematological malignancies in multiple ongoing earlier
stage clinical trials."
The Phase 3 MAESTRO study for TH-302 was initiated following results
from a randomized, controlled Phase 2b trial of TH-302 in patients
with pancreatic cancer. At the ESMO 2012 Congress (European Society
for Medical Oncology) updated results were presented confirming a
significant improvement (p=0.008) in PFS associated with 41%
reduction of risk for disease progression or death for patients
treated with TH-302 340 mg/m2. This represented a 2.4-month increase
in median PFS for patients receiving TH-302 340 mg/m2. The 12-month
overall survival rates were also in favor of the TH-302 340 mg/m2
treatment group compared with the control arm (38% vs 26% (p=0.13)).
The most common adverse events were fatigue, nausea and peripheral
edema, and were similar across groups. Skin and mucosal toxicities,
predominantly Grade 1 and 2, and myelosuppression, were the most
common adverse events related to TH-302 and did not result in
increases in treatment discontinuation. Adverse events leading to
discontinuation of study treatment as well as serious adverse events
were balanced across all treatment arms. Severe (Grade 3/4)
myelosuppression was more frequent compared to gemcitabine alone. All
other severe adverse events were generally below 10%.
It is estimated that approximately 277,000 cases of pancreatic cancer
are diagnosed worldwide every year, accounting for 2.2% of all
cancers. Pancreatic cancer is the eighth most common cancer in Europe
and the eleventh most common in the United States. Almost 67% of
cases are diagnosed in people aged 65 and over; it is uncommon in
people under the age of 40. Pancreatic cancer has a low survival rate
regardless of stage of disease, with almost 95% of patients dying
from their disease within 5 years. It is estimated that there are
around 266,000 deaths from pancreatic cancer worldwide each year.
About TH-302
TH-302 is an investigational hypoxia-targeted drug that is designed
to be activated under severe tumor hypoxic conditions, a hallmark of
many cancers. Areas of low oxygen levels (hypoxia) in solid tumors
are due to insufficient blood supply as a result of aberrant
vasculature. Similarly, the bone marrow of patients with
hematological malignancies has also been shown, in some cases, to be
severely hypoxic.
TH-302 is currently under evaluation in two Phase 3 trials: one in
combination with doxorubicin versus doxorubicin alone in patients
with soft tissue sarcoma (STS), and the other in combination with
gemcitabine versus gemcitabine and placebo in patients with advanced
pancreatic cancer. Both Phase 3 trials are being conducted under a
Special Protocol Assessment with the U.S. Food and Drug
Administration (FDA). The FDA and the European Commission have
granted TH-302 Orphan Drug Designation for the treatment of STS.
TH-302 is also being investigated in hematological malignancies and
combination trials in solid tumors.
Merck KGaA signed a global license and co-development agreement for
TH-302 with Threshold in February 2012, which includes an option for
Threshold to co-commercialize in the U.S.
About Threshold Pharmaceuticals, Inc.
Threshold Pharmaceuticals, Inc., is a biotechnology company focused
on the discovery and development of drugs targeting tumor hypoxia,
the low oxygen condition found in the microenvironments of most solid
tumors as well as the bone marrows of some patients with hematologic
malignancies. This approach offers broad potential to treat a variety
of cancers. By selectively targeting tumor cells, we are building a
pipeline of drugs that hold promise to be more effective and less
toxic to healthy tissues than conventional anticancer drugs. For
additional information, please visit our website
(www.thresholdpharm.com).
Forward-Looking Statements
Except for statements of historical fact, the statements in this
press release are forward-looking statements, including statements
regarding the potential therapeutic uses and benefits of TH-302 to
treat patients with pancreatic cancer, soft tissue sarcoma or other
cancers. These statements involve risks and uncertainties that can
cause actual results to differ materially from those in such
forward-looking statements. Potential risks and uncertainties
include, but are not limited to, the ability to enroll or complete
anticipated clinical trials, the time and expense required to conduct
such clinical trials and analyze data, whether later trials confirm
the results of earlier trials, whether the Phase 3 trial data is
sufficient to support regulatory approval to market TH-302, and
issues arising in the regulatory or manufacturing process and the
results of such clinical trials (including product safety issues and
efficacy results). Further information regarding these and other
risks is included under the heading "Risk Factors" in Threshold's
Quarterly Report on Form 10-Q, which has been filed with the
Securities and Exchange Commission on November 2, 2012 and is
available from the SEC's website (www.sec.gov) and on our website
(www.thresholdpharm.com) under the heading "Investors." We undertake
no duty to update any forward-looking statement made in this news
release.
Contact:
Laura Hansen, Ph.D.
Senior Director, Corporate Communications
Phone: 650-474-8206
E-mail: lhansen@thresholdpharm.com